Hasson: ku. Hasson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC. Abstract Envenoming by Echis saw-scaled viper is the leading cause of death and morbidity in Africa due to snake bite. Despite its medical importance, there have been few investigations into the toxin composition of the venom of this viper.

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Table 2 Comparison of amino acid motifs which are responsible for the potent effects and characterisation of some published venom serine proteases with the four EoSP cDNAs.

Figure 4 Amino acid sequence similarity between EoSP Variants and serine proteases from related vipers. The residues shaded in black correspond to residues that are identical to EoSP Activated peptide where the mature proteine cleaved is represented by green rectangle.

Predicted Antigenic Profile Analysis of E. The predicted antigenic profiles of the published and new E. The deduced signal peptide domains of the EoSP variants are separated by a vertical dotted line, as these would normally be cleaved from the native proteins during posttranslational. Figure 5 Comparison of antigenic profile of the EoSer variants with analogous serine proteases used in Figure 4. The top horizontal scale represents the number of amino acid residues.

The conserved signal peptide is separated from the mature protein by a vertical dotted line. The three vertical boxes were drawn to indicate the conserved catalytic traid regions described in the text.

Discussion Serine proteases are a major component of viper venoms and are thought to disrupt several distinct elements of the blood coagulation system of envenomed victims. A detailed understanding of the functions of these enzymes is important for both acquiring a full understanding of the pathology of envenoming and because these venom proteins have shown a vital role in treating blood coagulation disorders. The unique specificity of snake venom proteinases makes them potentially useful in research of fibrinogen-depletion and limited proteolysis [ 62 , 63 ].

This may be due to the existence of multiple forms of serine proteases in the venom of a single viper species which is likely to contribute to the diverse biological effects exerted by the whole venom. Therefore, screening the E. The results obtained in this work provide the first molecular sequence data for E.

The utilization of PCR amplification of E. To differentiate between the isolated EoSP clones a surface probability algorithm was used to assign the 14 E. A single representative clone from each group was chosen for further analyses as described earlier.

The greatest sequence similarity was between EoSer-7 and B. From the proteins with known biological activity, sequence similarities of the EoSP variants i. Comparison of the EoSP variants with analogous members of the serine protease family revealed that all EoSP variants encoded the presumed catalytic triad, which is common to venom serine proteases H67, D and S as shown in Figure 4.

Such residues were highly conserved in groups 1—3, except proteins of group 4 Figures 2 b and 4 which contain R instead of H at the same position Figure 4. Although such motifs are thought to be needed for protein stabilization rather than for the catalytic function of the venom enzymes [ 30 ], confirmation of the roles of such motifs in venom proteases remain to be investigated.

All serine proteases have a common pattern of 6-disulfide bridges [ 69 , 70 ]. They contain twelve cysteine residues, ten of which form five disulfide bonds, based on the homology with trypsin [ 64 ]; the remaining two cysteines form a unique and conserved bridge among SVSPs, involving Cyse chymotrypsinogen numbering , found in the C-terminal extension [ 35 ].

This suggests that the EoSP proteins possess a similar tertiary structure to that of other serine proteases which are well characterized. Despite such sequence and structural conservation, viper venom serine proteases show very divergent effects on haemostasis as previously stated. In some cases certain amino acid sequences have been shown to be responsible for such effects as demonstrated in Table 2. Although such table gives a preliminary prediction of the functional characterization of the EoSP cDNAs in comparison with well-known characterized venom serine proteases, it cannot be considered as a functional confirmation or even a categorization strategy to differentiate between the four EoSP cDNAs.

However, from Figure 4 and Table 2 it can be generally concluded that such comparison demonstrates that the enzymes encoded by the four EoSP cDNAs confer multiple haemostasis-disruptive activities to E.

Furthermore, the sequence and predicted structural similarities of these four EoSP groups suggest that an antibody generated to one group may be capable of neutralizing the other group of EoSPs.

To examine this permeability the sequences of EoSP groups were subjected to a more specific algorithm that predicted amino acid motifs of high immunogenicity. A protein structure-predicting algorithm [ 56 ] has been used i to identify domains of strong antigenic potential in the toxin gene product and ii to determine whether these domains are conserved in analogous venom toxin gene products of related vipers.

The signal peptide was separated from the mature protein by dotted line as would be cleaved posttranslationally. The peaks shown by the EoSPs profile indicate the numerous domains predicted to have a surface location and potential for antibody induction. Although the antigenic peaks of the catalytic traid of the EoSPs showed less similarity with that of the analogous venom SPs particularly those at residues 67 and , many antigenic residue similarities of EoSPs are shared with other SVSPs of related vipers.

Therefore, it is likely that antibodies raised by EoSP DNA immunisation are likely to possess considerable cross-reactivity and might competitively inhibit the function of these domains in the similar venom toxins of related vipers. However, binding of antibodies specific to conserved antigenic domains without a known function are equally as likely to disrupt protein function by virtue of steric hindrance.

The veracity of these speculations need to be confirmed experimentally and thus is a focus of our current research. This observation strongly suggests that an antibody raised by immunisation with group one EoSP DNA is likely to be less effective against the gene products of groups 2, 3, or 4. Therefore additional antibodies generated against antigenic index that showed less conservation will be required. The authors would like to thank Dr. Harrison, Prof. Theakston, and Mr.

Paul Rowley for their assistance during extraction of the venom glands from snakes and Dr. Nasidi, Federal Ministry of Health, Nigeria, for obtaining the snakes. References J. Theakston, and D. Trape, G. Pison, E. Guyavarch, and Y. View at: Google Scholar S. Wagstaff and R. Casewell, R. Harrison, W. Hasson, A. Al-Jabri, T. Sallam, M. Al-Balushi, and R. Menez, Ed.

View at: Google Scholar P. View at: Google Scholar A. Habib, S. Abubakar, I. Abubakar et al. Warrell, N. Davidson, and B. View at: Google Scholar M. Weinberg, L. Felicori, C. Bello et al. Sallau and M. View at: Google Scholar J. Howes, R. Theakston, and G. Liu, M. Sun, C. Sun, B. Zhao, F. Greenaway, and Q. Bharati, S. Hasson, J. Oliver, G. Laing, R. Theakston, and R. Lu, A. Navdaev, J. Clemetson, and K. Stocker, Ed. View at: Google Scholar T. Matsui, Y. Fujimura, and K.

Markland Jr. View at: Google Scholar H. Pirkle and K. Pirkle and I. Rucavado, L.


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